The aim of this work is to understand the manner in which the production of acetylcholinesterase is regulated in Drosophila. We are attracted to this system because it lends itself to sophisticated genetic manipulations, is biochemically accessible, and exhibits a tissue specific pattern of expression. Thus, questions about differential gene expression during development can be asked using this system. Our work for the next year will involve final purification of Drosophila acetylcholinesterase to homogeneity, isolation of a variety of conditional mutations on the basis of altered sensitivity to anticholinesterase agents (we are presently using the pesticides Bidrin and Malathion), isolation of Ace ion isoalleles and initial genetic and biochemical characterization of these alterations. We will also construct the proper genetic strains for future attempts to clone the acetylcholinesterase structural gene sequences by recombinant DNA techniques. However, recombinant DNA work will not be initiated in this next year.